Forced treadmill exercise can induce stress and increase neuronal damage in a mouse model of global cerebral ischemia.
Level 5 - mechanism / opinion, no new human data
Animal experimental study
PubMed 27981192 · doi:10.1016/j.ynstr.2016.09.002
What was done
C57BL/6 mice (n = 63) were assigned to either 4.5 weeks of forced treadmill running or a sedentary program prior to the induction of global cerebral ischemia. Behavioral outcomes (anxious, depressive, and cognitive behaviors) were analyzed alongside fecal corticosterone levels measured by ELISA. Brain damage and inflammatory responses were assessed using immunohistochemistry, multiplex electrochemoluminescence ELISA, and Western blot. A separate cohort of mice was evaluated with voluntary wheel running for comparison.
What was found
Forced treadmill exercise induced a stress response, resulting in increased anxiety in the Open Field test and elevated fecal corticosterone levels (no exact numbers provided in abstract). Mice subjected to forced exercise developed larger hippocampal neuronal damage and higher cytokine levels in brain and blood after ischemia compared to sedentary controls; damage severity correlated with corticosterone levels. In contrast, voluntary wheel running did not increase anxiety or corticosterone levels.
Why it matters
This study indicates that forced exercise pre-conditioning can trigger a detrimental stress response that worsens ischemic brain injury, highlighting the importance of stress as a confounding factor in exercise-induced neuroprotection.
Limits
This is an animal model of ischemia and cannot be directly translated to humans. The abstract does not report specific numerical values, confidence intervals, or p-values, nor does it specify the sample size for the voluntary running comparator cohort.
Cited by
- supports Mice forced to run on a treadmill exhibit elevated cortisol and reduced survival, whereas mice given voluntary access to running wheels show increased longevity.